Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse
Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36–40 wee...
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| Veröffentlicht in: | Inflammation 2024-12, Vol.47 (6), p.2173-2195 |
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| creator | Cai, Lu-Qiong Li, Xiu-Chun Wang, Yang-Yue Chen, Yu-Xin Zhu, Xia-Yan Zuo, Zi-Yi Si-Ma, Yi-Qun Lin, Yi-Nuo Li, Xiao-Kun Huang, Xiao-Ying |
| description | Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36–40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36–40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism. |
| doi_str_mv | 10.1007/s10753-024-02032-3 |
| format | Article |
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FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36–40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36–40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.</description><identifier>ISSN: 0360-3997</identifier><identifier>ISSN: 1573-2576</identifier><identifier>EISSN: 1573-2576</identifier><identifier>DOI: 10.1007/s10753-024-02032-3</identifier><identifier>PMID: 38653921</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Aging ; Aging - metabolism ; Amino acids ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Energy Metabolism ; Fatty liver ; Fatty Liver - metabolism ; Fatty Liver - pathology ; Fibroblast Growth Factors - genetics ; Fibroblast Growth Factors - metabolism ; Glucose metabolism ; Hepatocytes ; Immunology ; Inflammation - metabolism ; Inflammatory diseases ; Internal Medicine ; Lipid Metabolism ; Liver - metabolism ; Liver - pathology ; Metabolic Diseases - genetics ; Metabolic Diseases - metabolism ; Metabolic disorders ; Metabolism ; Metabolomics ; Mice ; Mice, Knockout ; Microvasculature ; Pathology ; Pharmacology/Toxicology ; Phenotypes ; Rheumatology ; Triglycerides</subject><ispartof>Inflammation, 2024-12, Vol.47 (6), p.2173-2195</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c426t-fd56e773c9e7c7a59b12b2dc9debdb14e9ff63dcb8712263316ebabea1bdd4333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10753-024-02032-3$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10753-024-02032-3$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38653921$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cai, Lu-Qiong</creatorcontrib><creatorcontrib>Li, Xiu-Chun</creatorcontrib><creatorcontrib>Wang, Yang-Yue</creatorcontrib><creatorcontrib>Chen, Yu-Xin</creatorcontrib><creatorcontrib>Zhu, Xia-Yan</creatorcontrib><creatorcontrib>Zuo, Zi-Yi</creatorcontrib><creatorcontrib>Si-Ma, Yi-Qun</creatorcontrib><creatorcontrib>Lin, Yi-Nuo</creatorcontrib><creatorcontrib>Li, Xiao-Kun</creatorcontrib><creatorcontrib>Huang, Xiao-Ying</creatorcontrib><title>Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse</title><title>Inflammation</title><addtitle>Inflammation</addtitle><addtitle>Inflammation</addtitle><description>Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36–40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36–40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.</description><subject>Aging</subject><subject>Aging - metabolism</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Energy Metabolism</subject><subject>Fatty liver</subject><subject>Fatty Liver - metabolism</subject><subject>Fatty Liver - pathology</subject><subject>Fibroblast Growth Factors - genetics</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Glucose metabolism</subject><subject>Hepatocytes</subject><subject>Immunology</subject><subject>Inflammation - metabolism</subject><subject>Inflammatory diseases</subject><subject>Internal Medicine</subject><subject>Lipid Metabolism</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Metabolic Diseases - genetics</subject><subject>Metabolic Diseases - metabolism</subject><subject>Metabolic disorders</subject><subject>Metabolism</subject><subject>Metabolomics</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Microvasculature</subject><subject>Pathology</subject><subject>Pharmacology/Toxicology</subject><subject>Phenotypes</subject><subject>Rheumatology</subject><subject>Triglycerides</subject><issn>0360-3997</issn><issn>1573-2576</issn><issn>1573-2576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUtv1TAQhS0EopfCH2CBLLFhE7A9jp2sUFW45YpWbICt5VdSl8QudlKp_x5fbimPBQtrFvPN8Zw5CD2n5DUlRL4plMgWGsJ4fQRYAw_QhrYSGtZK8RBtCAjSQN_LI_SklCtCSNd38BgdQSda6BndoK-7eOPLEka9hBRxGvCFX7RJU7BYR4d3cZj0POsl5Vv8LpSUnc84RLxcenwyhjji7dmWUfwxJvstrQu-SGvxT9GjQU_FP7urx-jL9v3n0w_N-aez3enJeWM5E0szuFZ4KcH2Xlqp295QZpizvfPGGcp9PwwCnDWdpIwJACq80cZrapzjAHCM3h50r1cze2d9XLKe1HUOs863Kumg_u7EcKnGdKMoFUQStld4daeQ0_e1nkLNoVg_TTr66kQB4S2lHBiv6Mt_0Ku05lj9KaDAaQ8dF5ViB8rmVEr2w_02lKh9buqQm6q5qZ-5qf0WL_70cT_yK6gKwAEotRVHn3___R_ZHyzlo_I</recordid><startdate>20241201</startdate><enddate>20241201</enddate><creator>Cai, Lu-Qiong</creator><creator>Li, Xiu-Chun</creator><creator>Wang, Yang-Yue</creator><creator>Chen, Yu-Xin</creator><creator>Zhu, Xia-Yan</creator><creator>Zuo, Zi-Yi</creator><creator>Si-Ma, Yi-Qun</creator><creator>Lin, Yi-Nuo</creator><creator>Li, Xiao-Kun</creator><creator>Huang, Xiao-Ying</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20241201</creationdate><title>Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse</title><author>Cai, Lu-Qiong ; Li, Xiu-Chun ; Wang, Yang-Yue ; Chen, Yu-Xin ; Zhu, Xia-Yan ; Zuo, Zi-Yi ; Si-Ma, Yi-Qun ; Lin, Yi-Nuo ; Li, Xiao-Kun ; Huang, Xiao-Ying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-fd56e773c9e7c7a59b12b2dc9debdb14e9ff63dcb8712263316ebabea1bdd4333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aging</topic><topic>Aging - metabolism</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Energy Metabolism</topic><topic>Fatty liver</topic><topic>Fatty Liver - metabolism</topic><topic>Fatty Liver - pathology</topic><topic>Fibroblast Growth Factors - genetics</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Glucose metabolism</topic><topic>Hepatocytes</topic><topic>Immunology</topic><topic>Inflammation - metabolism</topic><topic>Inflammatory diseases</topic><topic>Internal Medicine</topic><topic>Lipid Metabolism</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Metabolic Diseases - genetics</topic><topic>Metabolic Diseases - metabolism</topic><topic>Metabolic disorders</topic><topic>Metabolism</topic><topic>Metabolomics</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Microvasculature</topic><topic>Pathology</topic><topic>Pharmacology/Toxicology</topic><topic>Phenotypes</topic><topic>Rheumatology</topic><topic>Triglycerides</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cai, Lu-Qiong</creatorcontrib><creatorcontrib>Li, Xiu-Chun</creatorcontrib><creatorcontrib>Wang, Yang-Yue</creatorcontrib><creatorcontrib>Chen, Yu-Xin</creatorcontrib><creatorcontrib>Zhu, Xia-Yan</creatorcontrib><creatorcontrib>Zuo, Zi-Yi</creatorcontrib><creatorcontrib>Si-Ma, Yi-Qun</creatorcontrib><creatorcontrib>Lin, Yi-Nuo</creatorcontrib><creatorcontrib>Li, Xiao-Kun</creatorcontrib><creatorcontrib>Huang, Xiao-Ying</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Inflammation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cai, Lu-Qiong</au><au>Li, Xiu-Chun</au><au>Wang, Yang-Yue</au><au>Chen, Yu-Xin</au><au>Zhu, Xia-Yan</au><au>Zuo, Zi-Yi</au><au>Si-Ma, Yi-Qun</au><au>Lin, Yi-Nuo</au><au>Li, Xiao-Kun</au><au>Huang, Xiao-Ying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse</atitle><jtitle>Inflammation</jtitle><stitle>Inflammation</stitle><addtitle>Inflammation</addtitle><date>2024-12-01</date><risdate>2024</risdate><volume>47</volume><issue>6</issue><spage>2173</spage><epage>2195</epage><pages>2173-2195</pages><issn>0360-3997</issn><issn>1573-2576</issn><eissn>1573-2576</eissn><abstract>Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36–40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36–40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38653921</pmid><doi>10.1007/s10753-024-02032-3</doi><tpages>23</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aging Aging - metabolism Amino acids Animals Biomedical and Life Sciences Biomedicine Energy Metabolism Fatty liver Fatty Liver - metabolism Fatty Liver - pathology Fibroblast Growth Factors - genetics Fibroblast Growth Factors - metabolism Glucose metabolism Hepatocytes Immunology Inflammation - metabolism Inflammatory diseases Internal Medicine Lipid Metabolism Liver - metabolism Liver - pathology Metabolic Diseases - genetics Metabolic Diseases - metabolism Metabolic disorders Metabolism Metabolomics Mice Mice, Knockout Microvasculature Pathology Pharmacology/Toxicology Phenotypes Rheumatology Triglycerides |
| title | Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse |
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